Histological Diagnoses of Military Personnel Undergoing Lung Biopsy After Deployment to Southwest Asia.

INTRODUCTION: The current understanding of associations between lung disease and military deployment to Southwest Asia, including Iraq and Afghanistan, is both controversial and limited. We sought to clarify the relation between military deployment and biopsy-proven lung disease. METHODS: Retrospective data were analyzed for military personnel with non-neoplastic lung biopsies evaluated at the Armed Forces Institute of Pathology or Joint Pathology Center (January 2005 to December 2012). RESULTS: Of 391 subjects, 137 (35.0%) had deployed to Southwest Asia prior to biopsy. Compared to non-deployed subjects, those deployed were younger (median age 37 vs. 51 years) with higher representation of African Americans (30.0 vs. 16.9%). Deployed patients were more likely diagnosed with non-necrotizing granulomas (OR 2.4). Non-deployed subjects had higher frequency of idiopathic interstitial pneumonias, particularly organizing pneumonia. Prevalence of small airways diseases including constrictive bronchiolitis was low. CONCLUSIONS: This study provides a broader understanding of diversity of biopsy-proven non-neoplastic lung disease as it relates to military deployment to Southwest Asia and importantly did not show an increased prevalence of small airway disease to include constrictive bronchiolitis.

Epiplakin Is a Paraneoplastic Pemphigus Autoantigen and Related to Bronchiolitis Obliterans in Japanese Patients.

All plakin family proteins are known to be autoantigens in paraneoplastic pemphigus (PNP). In this study, we first examined whether PNP sera also react with epiplakin, another plakin protein, by various immunological methods using 48 Japanese PNP sera. Immunofluorescence confirmed that cultured keratinocytes expressed epiplakin. Epiplakin was detected by 72.9% of PNP sera by immunoprecipitation-immunoblotting with KU-8 cell extract, but not by immunoblotting of either normal human epidermal extract or KU-8 cell extract. Epiplakin was essentially not detected by 95 disease and normal control sera. Statistical analyses of various clinical and immunological findings revealed a significant correlation of the presence of anti-epiplakin antibodies with both bronchiolitis obliterans and mortality. No epiplakin-negative PNP case developed bronchiolitis obliterans. However, although 29.4% of European patients with PNP had bronchiolitis obliterans, significant correlation with anti-epiplakin autoantibodies was not observed. In further studies for lung, immunofluorescence showed the presence of epiplakin in normal human lung, particularly respiratory bronchiole, immunoprecipitation-immunoblotting showed that PNP sera reacted with epiplakin in cultured lung cells, and mice injected with polyclonal antibody specific to epiplakin histopathologically showed abnormal changes in small airway epithelia. These results indicated that epiplakin is one of the major PNP autoantigens and is related to PNP-related bronchiolitis obliterans.

Bronchiolitis obliterans and rheumatoid arthritis. Report of a case in a Chinese patient on d-penicillamine and review of the literature.

Rheumatoid arthritis is the commonest connective tissue disease associated with bronchiolitis obliterans, a clinico-pathologic entity of bronchiolar inflammation and fibrosis reflecting injury to the small airways, and presenting with symptoms and signs of small airways obstruction. It may arise de novo or as a complication of therapy due to d-penicillamine, when a distinct histologic picture of bronchiolar constriction without intraluminal inflammatory polyps appeared to be predominant in most reported cases. This condition is associated with a high morbidity and mortality, and apart from cessation of d-penicillamine, there are no standard recommendations for treatment. Response to various immunosuppressive agents, including corticosteroid, azathioprine, and cyclophosphamide, had been variable and unsatisfactory. We report a case of bronchiolitis obliterans in a Chinese female treated with d-Penicillamine for rheumatoid arthritis with the first documented response to corticosteroid alone, and review the literature on this subject.

Exudative bronchiolitis after lung transplantation.

BACKGROUND: After lung transplantation patients frequently develop small airways disease. Exudative bronchiolitis (EB) has not been described previously in this population. We describe a case series of patients who have developed EB after lung transplantation. METHODS: We reviewed the clinical records and radiologic data of 99 patients who underwent single and bilateral lung transplantation. Data relating to ethnicity, transplant indication, human leukocyte antigen (HLA) status, complications and survival were recorded. The EB cohort, defined by high-resolution computed tomographic (HRCT) evidence of the disease, was compared with a group of patients who had not developed EB. RESULTS: The majority of patients had chronic obstructive pulmonary disease (COPD; n = 51), followed by cystic fibrosis (CF; n = 22), pulmonary fibrosis (n = 8), pulmonary hypertension (n = 7), bronchiectasis (n = 5), lymphangioleiomyomatosis (n = 3) and Eisenmenger's syndrome (n = 3). Thirteen patients were found to have developed EB. EB was more commonly seen in Maori and Pacific Island patients (p < 0.05). EB was significantly associated with early infection post-transplant (p < 0.05) and a history of Aspergillus infection (p < 0.005) or diabetes (p < 0.05). The patients with EB were also significantly more likely to develop bronchiolitis obliterans syndrome (p < 0.0005), bronchiectasis (p < 0.0005) or small airways disease (p < 0.05). Patients with EB had a varied response to treatment, with the majority showing improvement. CONCLUSIONS: EB was noted to occur after lung transplantation in a significant proportion of patients, but will not be detected unless HRCT is used routinely. It has been associated with patients' ethnicity, donor haplotype, infection and the development of airways disease. EB may be a prominent indicator of the likelihood of developing BOS.